title: Combination chemotherapy with cisplatin and nifedipine: synergistic antitumor effects against a cisplatin-resistant subline of the B16 amelanotic melanoma.
abstract: Cisplatin has become one of the most commonly prescribed cytotoxic chemotherapeutic agents. Unfortunately, the cure rate is low due to the development or outgrowth of cisplatin-resistant cells which repopulate tumors, resulting in patient death. We reported previously that the calcium channel blocker nifedipine enhances the antitumour actions of cisplatin (cis-diamminedichloroplatinum (II] against murine tumors which are inherently cisplatin-sensitive (B16a) or inherently cisplatin-resistant (3LL). We have developed an induced cisplatin-resistant tumor variant (B16a-Pt) that is 30 times more resistant to cisplatin than its cisplatin-sensitive parent line. In short-term studies, we report that nifedipine significantly enhanced the cytotoxicity of cisplatin against primary B16a-Pt tumors and their spontaneous pulmonary metastases. In long term studies, we report that combination therapy with nifedipine and cisplatin results in significantly enhanced survival.
authors.affiliation: Department of Radiation Oncology, Wayne State University, Detroit, Michigan.
authors.forename: J M
authors.initials: JM
authors.lastname: Onoda
authors.forename: K K
authors.initials: KK
authors.lastname: Nelson
authors.forename: S M
authors.initials: SM
authors.lastname: Pilarski
authors.forename: N S
authors.initials: NS
authors.lastname: White
authors.forename: R G
authors.initials: RG
authors.lastname: Mihu
authors.forename: K V
authors.initials: KV
authors.lastname: Honn
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004351:Drug Resistance; D004357:Drug Synergism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008815:Mice, Inbred Strains; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects
chemical_list: D009543:Nifedipine; D002945:Cisplatin